Artemisia vulgaris Extract as a Novel Therapeutic Approach for Reversing Diabetic Cardiomyopathy in a Rat Model.

Diabetic cardiomyopathy, a severe diabetic complication, impairs heart function, leading to heart failure. Treatment that effectively addresses this condition without causing side effects is urgently needed. Current anti-hyperglycemic therapies are expensive, has side effects and do not effectively prevent cardiac remodeling. Therefore, it is important to explore natural products that may have the potential to reverse cardiac remodeling. That is why the aim of the current study was to determine the left ventricular remodeling potential of the methanolic extract of Artemisia vulgaris in a diabetic cardiomyopathy rat model. Following the initial comprehensive phytochemical evaluation of plant phenolic and flavonoid content, which showed strong anti-hyperglycemic and antioxidant activities, an extract of Artemisia vulgaris was administered in an in vivo experiment. Diabetic cardiomyopathy was induced in Wistar albino rats according to previously described protocols in the literature, and the effect of treatment was checked by serum and histopathological analysis after 45 days. Artemisia vulgaris treatment significantly (p ≤ 0.05) reduced fasting blood glucose (108.5 ± 1.75 mg/dL), glycated hemoglobin (4.03 ± 0.12 %), serum glucose (116.66 ± 3.28 mg/dL), insulin (15.66 ± 0.66 ng/mL), total oxidant status (54.66 ± 3.22 µmol H2O2Equiv.L-1), Malondialdehyde (0.20 ± 0.01 mmol/L), total cholesterol (91.16 ± 3.35 mg/dL), triglycerides (130.66 ± 3.15 mg/dL), low-density lipids (36.57 ± 1.02 mg/dL), sodium (140 ± 3.21 mmol/L), calcium (10.44 ± 0.24 mmol/L), creatine kinase MB (1227.5 ± 17.89 IU/L), lactate dehydrogenase (1300 ± 34.64 IU/L), C-reactive protein (30 ± 0.57 pg/mL), tumor necrosis factor-α (58.66 ± 1.76 pg/mL), atrial natriuretic peptide (2.53 ± 0.04 pg/mL), B-type natriuretic peptide (10.66 ± 0.44 pg/mL), aspartate aminotransferase (86.5 ± 4.99 U/L), Alanine Transaminase (55.33 ± 2.90 U/L), urea (25.33 ± 1.15 mg/dL) and creatinine (0.64 ± 0.02 mg/dL) but significantly increased (p ≤ 0.05) total antioxidant capacity (1.73 ± 0.07 mmol Trolox Equil./L), high-density lipids (40 ± 1.59 mg/dL) and potassium (3.82 ± 0.04 mmol/L) levels. ECG and histopathology confirmed the significant improvement in remodeling and the reversal of structural changes in the heart and pancreas. In conclusion, Artemisia vulgaris possesses significant left ventricular remodeling potential in course of diabetes-induced cardiomyopathy.

Curative effects of tectochrysin on paraquat-instigated testicular toxicity in rats: A biochemical and histopathological based study.

Background: Paraquat (PQ) is a herbicide that is used globally in the agriculture sector to eradicate unwanted weeds, however it also induces significant damages in various organs of the body such as testes. Tectochrysin (TEC) is an important flavonoid that shows versatile therapeutic potentials. Currently, there is no established antidote to cure PQ-induced testicular toxicity. Objective: The present study was conducted to evaluate the ameliorative effects of TEC against PQ prompted testicular damage. Methods: Sprague-Dawley rats (n = 48) were used to conduct the trial. Rats were allocated in to 4 groups i.e., Control, PQ administrated group (5 mgkg-1), PQ + TEC co-administrated group (5 mgkg-1 + 2.5 mgkg-1) and TEC only administrated group (2.5 mgkg-1). The trial was conducted for 8 weeks. The activity of anti-oxidants and the levels of MDA and ROS were determined by spectrophotometric method. Steroidogenic enzymes as well as apoptotic markers expressions were evaluated by qRT-PCR. The level of hormones and inflammatory indices was quantified by enzyme-linked immunosorbent assay. Results: PQ exposure markedly (P < 0.05) disturbed the biochemical, spermatogenic and histological profile in the rats. Nevertheless, TEC treatment considerably (P < 0.05) increased CAT, GPx GSR and SOD activity, besides decreasing MDA and ROS contents. TEC administration also increased sperm viability, count and motility. 17ß-HSD, 3ß-HSD, StAR and Bcl-2 expressions were also increased following TEC administration. The supplementation of TEC substantially (P < 0.05) decreased Bax, Caspase-3 expression and the levels of inflammatory markers i.e., interleukin-1ß (IL-1ß), interleukin-6 (IL-6), nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) activity. Additionally, the levels of plasma testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were increased following TEC supplementation. Furthermore, TEC supplementation considerably decreased sperm structural abnormalities and histomorphological damages of the testes. The mitigative role of TEC might be due to its anti-inflammatory, anti-apoptotic, androgenic and anti-oxidant potentials. Conclusion: Taken together, it is concluded that TEC can be used as a potential candidate to treat testicular toxicity.

Alleviative effects of pinostrobin against cadmium-induced renal toxicity in rats by reducing oxidative stress, apoptosis, inflammation, and mitochondrial dysfunction.

Introduction: Cadmium (Cd) is a highly toxic heavy metal that can be found everywhere in the environment and can have harmful effects on both human and animal health. Pinostrobin (PSB) is a bioactive natural flavonoid isolated from Boesenbergia rotunda with several pharmacological properties, such as antiinflammatory, anticancer, antioxidant, and antiviral. This investigation was intended to assess the therapeutic potential of PSB against Cd-induced kidney damage in rats. Methods: In total, 48 Sprague Dawley rats were divided into four groups: a control, a Cd (5 mg/kg), a Cd + PSB group (5 mg/kg Cd and 10 mg/kg PSB), and a PSB group (10 mg/kg) that received supplementation for 30 days. Results: Exposure to Cd led to a decrease in the activities of catalase (CAT), glutathione reductase (GSR), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX), whereas levels of reactive oxygen species (ROS) and malondialdehyde (MDA) increased. Cd exposure also caused a substantial increase in urea, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and creatinine levels. Moreover, a noticeable decline was noticed in creatinine clearance. Moreover, Cd exposure considerably increased the levels of inflammatory indices, including interleukin-1b (IL-1b), tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), nuclear factor kappa-B (NF-kB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) activity. Cd treatment decreased the expression of the antiapoptotic markers (Bcl-2) while increasing the expression of apoptotic markers (Bax and Caspase-3). Furthermore, Cd treatment substantially reduced the TCA cycle enzyme activity, such as alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, and isocitrate dehydrogenase. Moreover, mitochondrial electron transport chain enzymes, succinatedehydrogenase, NADH dehydrogenase, cytochrome c-oxidase, and coenzyme Q-cytochrome reductase activities were also decreased following Cd exposure. PSB administration substantially reduced the mitochondrial membrane potential while inducing significant histological damage. However, PSB treatment significantly reduced Cd-mediated renal damage in rats. Conclusion: Thus, the present investigation discovered that PSB has ameliorative potential against Cd-induced renal dysfunction in rats.

Attenuative effect of astilbin on polystyrene microplastics induced testicular damage: Biochemical, spermatological and histopathological-based evidences.

Polystyrene microplastics (PS-MPs) are the potential environmental pollutants that possess the ability to induce testicular damage. Astilbin (ASB) is a dihydroflavonol, abundantly reported in multiple plants that has various pharmacological properties. This research elucidated the mitigative potential of ASB against PS-MPs-instigated testicular toxicity. 48 adult male rats (200 ± 10 g) were distributed into 4 groups (n = 12): control, PS-MPs received (0.01 mg/kg), PS-MPs + ASB received (0.01 mg/kg + 20 mg/kg) and ASB supplemented group (20 mg/kg). After 56th day of the trial, animals were sacrificed and testes were harvested for the estimation of biochemical, hormonal, spermatogenic, steroidogenic, apoptotic and histological profiles. PS-MPs intoxication significantly (P < 0.05) lowered glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione reductase (GSR) as well as catalase (CAT) activities, whereas elevated MDA as well as ROS levels. Besides, the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), nuclear factor kappa-B (NF-κB) along with cyclooxygenase-2 (COX-2) activity were raised. PS-MPs treatment reduced luteinizing hormone (LH), plasma testosterone and follicle-stimulating hormone (FSH) level besides decreased epididymal sperm number, viability, motility as well as the count of HOS coil-tailed spermatozoa and increased sperm morphological irregularities. PS-MPs exposure lowered steroidogenic enzymes (17ß-HSD, 3ß-HSD and StAR protein along with Bcl-2 expression, besides increasing Caspase-3 and Bax expressions and histopathological alterations in testicular tissues. However, ASB treatment significantly reversed PS-MPs mediated damage. In conclusion, ASB administration is protective against PS-MPs-instigated testicular damage owing to its anti-inflammatory, anti-apoptotic, antioxidant and androgenic nature.

Rhamnetin alleviates polystyrene microplastics-induced testicular damage by restoring biochemical, steroidogenic, hormonal, apoptotic, inflammatory, spermatogenic and histological profile in male albino rats.

The current research was performed to evaluate the ameliorative effects of Rhamnetin (RHM) on polystyrene microplastics (PS-MPs)-instigated testicular dysfunction in male albino rats. 48 albino rats were distributed in four groups, i.e., control, PS-MPs treated, PS-MPs + RHM co-treated and RHM only supplemented group. PS-MPs exposure considerably reduced anti-oxidant enzymes i.e., catalase (CAT), glutathione peroxidase (GSR), superoxide dismutase (SOD) and glutathione reductase (GPx) activities. Whereas, reactive oxygen species (ROS) level along with malondialdehyde (MDA) was considerably escalated in PS-MPs treated rats as well as a potential decline was observed in sperm progressive motility. Additionally, a substantial upsurge was noticed in the count of dead sperms, deformity in the tail, mid-piece and head of sperms in PS-MPs treated rats. PS-MPs exposure also decreased steroidogenic enzymes, 17ß-hydroxysteroid dehydrogenase (17ß-HSD), steroidogenic acute regulatory protein (StAR) and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) expressions. Moreover, the levels of inflammatory indices i.e., Interleukin-6 (IL-6), Nuclear factor kappa-B (NF-κB), Interleukin-1ß (IL-1ß), tumour necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) activity were also increased in PS-MPs administrated group. Besides it increased the expression of apoptotic markers (Bax and caspase-3) expression. Whereas, anti-apoptotic marker i.e., Bcl-2 expression was reduced. Moreover, luteinizing hormone (LH), follicle-stimulating hormone (FSH) as well as plasma testosterone levels were also decreased. PS-MPs exposure also led to a substantial histopathological damage in testicular tissues. However, RHM supplementation potentially reduced the damaging effects of PS-MPs in the reproductive tissues of male albino rats. Thus, the current study revealed, RHM possesses potential to prevent PS-MPs-induced testicular damage due to its anti-oxidant anti-apoptotic, anti-inflammatory as well as androgenic properties.

Analyzing cross-talk of EPO and EGF genes along with evaluating therapeutic potential of Cinnamomum verum in cigarette-smoke-induced lung pathophysiology in rat model.

The integrity of the distal alveolar epithelium is crucial for lung regeneration following an injury. The present study aimed to evaluate the effect of Cinnamomum verum extract; cross-talk of epidermal growth factor (EGF) and erythropoietin (EPO) genes in a smoke-induced lung injury rat model. For experimentation (n = 27), albino rats were divided equally into three groups, i.e., negative control (NC), positive control (PC), and treatment group (TG). Cigarette smoke was exposed to PC and TG (4 CG/day). C. verum was given orally (350 mg/kg body weight) for 21 days. Decapitation (n = 3) was done on 14th, 18th, and 21st days, respectively. Analyses (hematology, biochemical, high performance liquid chromatography [HPLC], histology, and gene expression) were carried out and results were statistically analyzed by two-way analysis of variance. HPLC analysis of ethanolic extract of C. verum was done to identify the presence of phenolic constituents which showed high concentrations of quercetin and P-coumaric acid. Serum oxidative parameters such as total oxidant status, malondialdehyde, and hematological parameters such as red blood cells, hemoglobin, hematocrit, and white blood cells were significantly (p < .05) elevated in the PC group; however, these parameters were significantly (p < .05) improved in TG. While total antioxidant capacity and serum parameters such as total protein, albumin, and globulin were significantly (p < .05) reduced in the PC group but significantly improved (p < .05) in TG. Histological analysis revealed that smoke exposure resulted in a measurable increase in alveolar septal thickening while ethanolic extract of C. verum greatly ameliorated the histopathological changes in the lung alveoli. The gene expression analysis of EGF and EPO genes showed a significant upregulation (p < .05) of both genes in PC group while in TG, the level of both genes downregulated, in which lung damage was ameliorated due to cytoprotective effects of ethanolic extract of C. verum.

Condiment Recipes Lead to Reduced Generation of Carcinogenic Polycyclic Aromatic Hydrocarbons in Duck Variety Meat During Charcoal Grilling.

The current study aimed to evaluate the impact of charcoal grilling in the generation of various polycyclic aromatic hydrocarbons in the tissues of 5 different organs (leg, chest, wings, liver, and heart) of falcated ducks (Mareca falcata) before and after pasting them with different condiment recipes (R1, R2, R3, and R4). All condiment-pasted and control samples before/after charcoal grilling were pursued in RP-HPLC for quantification of unknown PAHs. Tissues from grilled raw leg meat of the control sample showed significantly higher (P ≤ .05) concentration (42.40 ng/g) of overall PAHs as compared to all other grilled samples. However, overall PAHs concentration (9.99 ng/g) in charcoal grilled tissues of leg meat pasted with R4 condiment recipe was decreased 76.43% significantly (P ≤ .05) as compared to all other recipes of pasted charcoal grilled samples. All PAHs, particularly naphthalene, fluorene, phenanthrene, and acenaphthalene were decreased significantly (P ≤ .05) to none detectable level in all tissue samples when grilled after treating with R4 condiment recipe. All condiment recipes reduced total PAHs level below MRL's set by the international guidelines. Recipe R4, a rich source of antioxidants, significantly neutralized and reduced the generation of PAHs in duck leg meat tissue sample during wood charcoal grilling.

Axonal Regeneration: Underlying Molecular Mechanisms and Potential Therapeutic Targets.

Axons in the peripheral nervous system have the ability to repair themselves after damage, whereas axons in the central nervous system are unable to do so. A common and important characteristic of damage to the spinal cord, brain, and peripheral nerves is the disruption of axonal regrowth. Interestingly, intrinsic growth factors play a significant role in the axonal regeneration of injured nerves. Various factors such as proteomic profile, microtubule stability, ribosomal location, and signalling pathways mark a line between the central and peripheral axons' capacity for self-renewal. Unfortunately, glial scar development, myelin-associated inhibitor molecules, lack of neurotrophic factors, and inflammatory reactions are among the factors that restrict axonal regeneration. Molecular pathways such as cAMP, MAPK, JAK/STAT, ATF3/CREB, BMP/SMAD, AKT/mTORC1/p70S6K, PI3K/AKT, GSK-3ß/CLASP, BDNF/Trk, Ras/ERK, integrin/FAK, RhoA/ROCK/LIMK, and POSTN/integrin are activated after nerve injury and are considered significant players in axonal regeneration. In addition to the aforementioned pathways, growth factors, microRNAs, and astrocytes are also commendable participants in regeneration. In this review, we discuss the detailed mechanism of each pathway along with key players that can be potentially valuable targets to help achieve quick axonal healing. We also identify the prospective targets that could help close knowledge gaps in the molecular pathways underlying regeneration and shed light on the creation of more powerful strategies to encourage axonal regeneration after nervous system injury.

Ameliorative effect of herbacetin against cyclophosphamide-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction.

Herbacetin (HBN) is a glycosylated flavonoid, which possesses numerous pharmacological properties. Cyclophosphamide (CYC) is a chemotherapeutic drug that adversely affects the kidneys. The present investigation aimed to evaluate the curative potential of HBN against CYC-induced nephrotoxicity. Sprague Dawley rats (n = 48) were randomly divided into four groups: control (0.1% DMSO + food), CYC (150 mg/kg b.wt.), CYC+HBN (150 + 40 mg/kg b.wt.), and HBN (40mg/kg b.wt.). CYC treatment significantly decreased the activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GSR) while elevating the concentration of reactive oxygen species (ROS) and malondialdehyde (MDA). Treatment with HBN significantly recovered the activity of CAT, SOD, GPx, and GSR while reducing the concentrations of ROS and MDA. Moreover, an increase in the level of renal functional markers, including Urea, creatinine, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL), and a decrease in creatinine clearance after CYC administration was recovered to control values by HBN treatment. Furthermore, HBN treatment normalized the increased levels of inflammatory markers such as nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) after CYC administration. Besides, HBN administration increased the expression of anti-apoptotic markers (Bcl-2) while decreasing the apoptotic markers (Bax and Caspase-3). Furthermore, HBN decreased the activities of tricarboxylic acid (TCA) cycle enzymes (ICDH, αKGDH, SDH, and MDH) as well as renal mitochondrial respiratory-chain complexes (I-IV) and repolarized mitochondrial membrane potential (ΔΨm). Additionally, HBN administration significantly protected against renal histological damage induced by CYC. In conclusion, CYC-induced toxicity was effectively ameliorated by the HBN administration. These results indicate that HBN might be considered as a potential protective agent against nephrotoxicity. The observed protection may be due to its antioxidant, anti-inflammatory, and anti-apoptotic potential.

Potential Therapeutic Benefits of Honey in Neurological Disorders: The Role of Polyphenols.

Honey is the principal premier product of beekeeping familiar to Homo for centuries. In every geological era and culture, evidence can be traced to the potential usefulness of honey in several ailments. With the advent of recent scientific approaches, honey has been proclaimed as a potent complementary and alternative medicine for the management and treatment of several maladies including various neurological disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis, etc. In the literature archive, oxidative stress and the deprivation of antioxidants are believed to be the paramount cause of many of these neuropathies. Since different types of honey are abundant with certain antioxidants, primarily in the form of diverse polyphenols, honey is undoubtedly a strong pharmaceutic candidate against multiple neurological diseases. In this review, we have indexed and comprehended the involved mechanisms of various constituent polyphenols including different phenolic acids, flavonoids, and other phytochemicals that manifest multiple antioxidant effects in various neurological disorders. All these mechanistic interpretations of the nutritious components of honey explain and justify the potential recommendation of sweet nectar in ameliorating the burden of neurological disorders that have significantly increased across the world in the last few decades.

Ziziphus Oxyphylla hydro-methanolic extract ameliorates hypertension in L-NAME induced hypertensive rats through NO/cGMP pathway and suppression of oxidative stress related inflammatory biomarkers.

ETHNOPHARMACOLOGICAL RELEVANCE: Ziziphus Oxyphylla belongs to family Ziziphus and has been used traditionally in hypertension. It is enriched with quercetin and kaempferol derivatives, catechin and cyclopeptide alkaloids. AIM: The current research evaluates the antihypertensive potential of aqueous methanolic extract of Z. oxyphylla (AMEZO) in NG-nitro-L-arginine methyl ester (LNAME) induced hypertension in rats. MATERIAL AND METHODOLOGY: Phytochemical analysis of AMEZO was carried out using high performance liquid chromatography (HPLC) and electrospray ionization mass spectrometry (ESI-MS/MS). Antihypertensive activities of AMEZO (200 and 400 mg/kg) and Kaempferol were assessed in L-NAME (185 µmol/kg, intraperitoneal) injected hypertensive rats. In normotensive rats, blood pressure was assessed using Power Lab data system. Serum and tissue samples were preserved for estimation of nitric oxide (NO), Cyclic guanosine monophosphate (cGMP), interleukin-6 (IL-6), tumor necrosis factor (TNF- α) and oxidative stress markers respectively. mRNA levels of eNOS, ACE, COX-2 and NF-kB genes were assessed through qPCR. RESULTS: The HPLC and ESI-MS/MS identified kaempferol, quercetin, catechin, ceanothic acid, zizybernalic acid and oxyphylline F. Chronic administration of AMEZO and kaempferol in L-NAME induced hypertensive rats significantly (p < 0.001) reduced systolic, diastolic and mean blood pressure. AMEZO and kaempferol caused meaningfully improved (p < 0.001) serum NO and cGMP levels. AMEZO administration also noticeably decrease the elevated IL-6 and TNF- α concentration in hypertensive animals. Administration of AMEZO and kaempferol also improved oxidative stress markers (MDA, CAT, SOD, GSH). The antihypertensive activity of AMEZO also resulted in upregulation of eNOS and downregulation of ACE. CONCLUSION: These data depict that AMEZO and kaempferol showed antihypertensive activity in LNAME induced hypertensive rats possibly mediated through improvement in NO and cGMP levels, modulation of mRNA expression of eNOS, ACE, COX-2 and NF-kB and suppression of oxidative stress related inflammatory markers, proposing a defensive role in cardiovascular diseases.

Efficacy of Euphorbia helioscopia in context to a possible connection between antioxidant and antidiabetic activities: a comparative study of different extracts.

BACKGROUND: Euphorbia helioscopia, conventionally known as sun spurge, has been used as a traditional medicine to treat different diseases owing to its reported antitumor, antiviral and antioxidant activities. METHODS: The current research was formulated to assess the in-vitro antioxidant and antidiabetic ability of Euphorbia helioscopia subsequent to the phytochemical analysis of its various extracts. For this purpose, methanol, ethanol and aqueous extracts were prepared using the whole dried plant. Phytochemical analysis of the extracts was done to evaluate the total flavonoid components (TFC) and total phenolic components (TPC) in the extracts. A total of seven phenolic and three flavonoid contents were documented and quantified using HPLC. Antioxidant values were found by DPPH● assay, FRAP and ABTS assays. The antidiabetic potential of the extracts was evaluated by measuring the inhibition ability of the activity of enzymes α amylase and α glucosidase. RESULTS: After analyzing statistically, the results showed that methanolic extract possesses the highest TFC and TPC values while aqueous extract encompassed the lowest level of these contents. Invitro results showed that methanolic extract of the Euphorbia helioscopia has the maximum antioxidant capability since it showed the highest scavenging ability towards the DPPH● (IC50 value = 0.06 ± 0.02 mg/ml), FRAP (758.9 ± 25.1 µMFe+ 2/g), and ABTS (689 ± 25.94 µMTEq/g) due to the presence of high TPC (24.77 ± 0.35 mgGAEq/g) and TFC (17.95 ± 0.32 mgQEq/g) values. Antidiabetic activity in terms of inhibition potential of α amylase and α glucosidase activity was also observed maximum in methanolic extract having lowest IC50 value (0.4 ± 0.01 mg/ml and 0.45 ± 0.01 mg/ml respectively) and minimum in the aqueous extract (IC50 value = 0.57 ± 0.02 mg/ml and 0.76 ± 0.1 mg/ml respectively). CONCLUSION: The experiment outcomes have shown that Euphorbia helioscopia extracts used in the current study contain antioxidant and antidiabetic activities; however, it is highest in its methanolic extract. The presence of the same trend towards the highest antidiabetic activity of the methanolic extract in terms of maximum inhibiting activity of α amylase and α glucosidase enzymes suggests a close association of TFC and TPC in minimizing diabetes.

Jaceosidin: A Natural Flavone with Versatile Pharmacological and Biological Activities.

Nature always remains an inexhaustible source of treasures for mankind. It remains a mystery for every challenge until the completion of the challenge. While we talk about the complicated health issues, nature offers us a great variety of chemical scaffolds and their various moieties packed in the form of natural products e.g., plants, microorganisms (fungi, algae, protozoa), and terrestrial vertebrates and invertebrates. This review article is an update about jaceosidin, a bioactive flavone, from genus Artemisia. This potentially active compound exhibits a variety of pharmacological activities including anti-inflammatory, anti-oxidant, anti-bacterial, antiallergic and anti-cancer activities. The bioactivities and the therapeutic action of jaceosidin, especially the modulation of different cell signaling pathways (ERK1/2, NF-κB, PI3K/Akt and ATM-Chk1/2) which become deregulated in various pathological disorders, have been focused here. The reported data suggest that the bioavailability of this anti-cancer compound should be enhanced by utilizing various chemical, biological and computational techniques. Moreover, it is recommended that researchers and scientists should work on exploring the mode of action of this particular flavone to precede it further as a potent anti-cancer compound.

Impact of different omega-3 fatty acid sources on lipid, hormonal, blood glucose, weight gain and histopathological damages profile in PCOS rat model.

BACKGROUND: Omega-3 fatty acids (Ω-3 PUFAs) may help to improve health status in polycystic ovarian syndrome (PCOS) by reducing numerous metabolic disorders (insulin sensitivity, hyperinsulinemia, lipid profile, obesity and inflammation). To evaluate the current objective, 16 weeks (6 weeks of adjustment period followed by 10 weeks of collection period) research trial was planned to check the impact of different sources of Ω-3 PUFAs (synthetic Ω-3, flaxseed and fish oil) on nutrient digestibility, weight gain, productive (lipid profile, glucose and insulin), reproductive profile (progesterone, follicle stimulating hormone (FSH), estrogen, luteinizing hormone (LH) and prolactin) and histological study of ovarian tissues in Wistar female rats. METHODS: Forty-five rats of 130 ± 10 g weight were divided into 5 groups, each having 9 rats: NC (negative control without PCOS), PC (positive control with PCOS), SO (synthetic omega-3 containing ALA, EPA and DHA), FO (flaxseed oil) and F (fish oil) fed at 300 mg/kg/orally/daily of these sources were added in the basal diets while PC and NC received only the basal diet. Food and water were offered ad libitum. PCOS was induced in the rats fed of PC, SO, FO and F diets group by single intramuscular injection of estradiol-valerate (4 mg/rat/IM). Body weight and blood glucose was recorded weekly. At 16th week of trial, blood samples were collected for lipid and hormonal analysis. Ovarian tissues were removed for pathological evaluation. Digestibility was measured by total collection method. RESULTS: Cholesterol, triglycerides and low-density lipoproteins were reduced in SO, FO and F groups when compared with rats of PC group. However, increasing trend of high-density lipoprotein (HDL) was found in same groups. The highest HDL (36.83 ± 0.72 mg/dL) was observed in rats fed F diet. In case of a hormonal profile, testosterone, LH and insulin levels showed a significant reduction after treatments. Blood glucose results showed significantly reducing trend in all the rats fed with Ω-3 PUFAs sources than PC from 5 to 10th week of trial. However, similar trend was noticed in rat's body weight at the end of 6th week. In ovarian morphology, different stages of follicles were observed in groups fed SO, FO and F diets. Nutrient digestibility in PCOS induced rats was remained non-significant. CONCLUSIONS: The three sources of Ω-3 PUFAs had effective role in improving lipid and hormonal profile, reducing blood glucose, weight gain and histopathological damages in PCOS rats. However, fish oil source might be an innovative approach to cure PCOS via reducing the weight and metabolic anomalies due to EPA and DHA.

Ginkgetin: A natural biflavone with versatile pharmacological activities.

Natural products, being richly endowed with curative powers, have become spotlight for biomedical and pharmaceutical research to develop novel therapeutics during recent years. Ginkgetin (GK), a natural non-toxic biflavone, has been shown to exhibit anti-cancer, anti-inflammatory, anti-microbial, anti-adipogenic, and neuroprotective activities. GK combats cancer progression by arresting cell cycle, inducing apoptosis, stimulating autophagy, and targeting many deregulated signaling pathways such as JAK/STAT and MAPKs. GKhalts inflammation mediators like interleukins, iNOS, COX-2, PGE2, NF-κB, and acts as an inhibitor of PLA2. GK shows strong neuroprotection against oxidative stress-promoted cell death, inhibits cerebral micro-hemorrhage, decreases neurologic deficits, and halts apoptosis of neurons. GK also acts as anti-fungal, anti-viral, anti-bacterial, leishmanicidal and anti-plasmodial agent. GK shows substantial preventive or therapeutic effects in in vivo models of many diseases including atherosclerosis, cancer, neurodegenerative, hepatic, influenza, and inflammatory diseases. Based on various computational, in vitro and in vivo evidences, this article demonstrates the potential of ginkgetin for development of therapeutics against various diseases. Although GK has been systematically studied from pharmacological point of view, a vast field of pharmacokinetics, pre-clinical and clinical studies is still open for the researchers to fully validate its potential for the treatment of various diseases.

Oleandrin: A bioactive phytochemical and potential cancer killer via multiple cellular signaling pathways.

Nerium oleander, a member of family Apocynaceae, is commonly known as Kaner in various countries of Asia and Mediterranean region. This plant has been renowned to possess significant therapeutic potential due to its various bioactive compounds which have been isolated from this plant e.g., cardiac glycosides, oleandrin, α-tocopherol, digitoxingenin, urosolic acid, quercetin, odorosides, and adigoside. Oleandrin, a saponin glycoside is one of the most potent and pharmacologically active phytochemicals of N. oleander. Its remarkable pharmacotherapeutic potential have been interpreted as anticancer, anti-inflammatory, anti-HIV, neuroprotective, antimicrobial and antioxidant. This particular bioactive entity is known to target the multiple deregulated signaling cascades of cancer such as NF-κB, MAPK, and PI3K/Akt. The main focus of the current study is to comprehend the action mechanisms of oleandrin against various pathological conditions. The current review is a comprehensive summary to facilitate the researchers to understand the pharmacological position of the oleandrin in the arena of drug discovery, representing this compound as a new drug candidate for further researches. Moreover, in vivo and in silico based studies are required to explore the mechanistic approaches regarding the pharmacokinetics and biosafety profiling of this compound to completely track its candidature status in natural drug discovery.

Salvianolic acid A & B: potential cytotoxic polyphenols in battle against cancer via targeting multiple signaling pathways.

Nature has generously offered life-saving therapies to mankind by providing evolutionarily optimized drug-like entities in the form of natural products. These splendid gifts of nature have served as most suitable candidates for anti-cancer drug discovery due to their pleiotropic activity on target molecules. This review aims to provide an update on the natural sources and bioactivities of such gifts from nature, salvianolic acid A & B, which are major bioactive constituents of a traditional Chinses medicinal herb, Salvia miltiorrhiza. Salvianolic acid A & B have been reported to owe anti-cancer, anti-inflammatory and cardioprotective activities. Currently salvianolic acids have been emerged as potent anti-cancer molecules. Salvianolic acid A & B fight cancer progression by prompting apoptosis, halting cell cycle and adjourning metastasis by targeting multiple deregulated signaling networks of cancer. Moreover, salvianolic acid A & B display potency towards sensitizing cancer cells to chemo-drugs. The review purposes that salvianolic acid A & B supply a novel opportunity for drug discovery but further experimentation is mandatory to embellish the knowledge of their pharmacological usage and to access their toxicological limits in order to establish these compounds as potential multitarget future drugs.

Putative Roles of Plant-Derived Tannins in Neurodegenerative and Neuropsychiatry Disorders: An Updated Review.

Neurodegenerative and neuropsychiatric diseases are characterized by the structural and functional abnormalities of neurons in certain regions of the brain. These abnormalities, which can result in progressive neuronal degeneration and functional disability, are incurable to date. Although comprehensive efforts have been made to figure out effective therapies against these diseases, partial success has been achieved and complete functional recovery is still not a reality. At present, plants and plant-derived compounds are getting more attention because of a plethora of pharmacological properties, and they are proving to be a better and safer target as therapeutic interventions. This review aims to highlight the roles of tannins, 'the polyphenol phytochemicals', in tackling neurodegenerative diseases including Alzheimer's and Parkinson's diseases as well as neuropsychiatric disorders like depression. Among the multifarious pharmacological properties of tannins, anti-oxidative, anti-inflammatory, and anti-cholinesterase activities are emphasized more in terms of neuroprotection. The current review also throws light on mechanistic pathways by which various classes of tannins execute neuroprotective effects. Despite their beneficial properties, some harmful effects of tannins have also been elaborated.

Role of Plant-Derived Flavonoids and Their Mechanism in Attenuation of Alzheimer's and Parkinson's Diseases: An Update of Recent Data.

Neurodegeneration is a progressive loss of neuronal cells in certain regions of the brain. Most of the neurodegenerative disorders (NDDs) share the communal characteristic such as damage or reduction of various cell types typically including astrocytes and microglial activity. Several compounds are being trialed to treat NDDs but they possess solitary symptomatic advantages along with copious side effects. The finding of more enthralling and captivating compounds to suspend and standstill the pathology of NDDs will be considered as a hallmark of present times. Phytochemicals possess the potential to alternate the synthetic line of therapy against NDDs. The present review explores the potential efficacy of plant-derived flavonoids against most common NDDs including Alzheimer's disease (AD) and Parkinson's disease (PD). Flavonoids are biologically active phytochemicals which possess potential pharmacological effects, including antiviral, anti-allergic, antiplatelet, anti-inflammatory, anti-tumor, anti-apoptotic and anti-oxidant effects and are able to attenuate the pathology of various NDDs through down-regulating the nitric oxide (NO) production, by reducing the tumor necrosis factor-α (TNF-α), by reducing the excitotoxicity of superoxide as well as acting as tyrosine kinase (TK) and monoamine oxidase (MAO) inhibiting enzyme.

Role of Plant Derived Alkaloids and Their Mechanism in Neurodegenerative Disorders.

Neurodegenerative diseases are conventionally demarcated as disorders with selective loss of neurons. Conventional as well as newer molecules have been tested but they offer just symptomatic advantages along with abundant side effects. The discovery of more compelling molecules that can halt the pathology of these diseases will be considered as a miracle of present time. Several synthetic compounds are available but they may cause several other health issues. Therefore, natural molecules from the plants and other sources are being discovered to replace available medicines. In conventional medicational therapies, several plants have been reported to bestow remedial effects. Phytochemicals from medicinal plants can provide a better and safer alternative to synthetic molecules. Many phytochemicals have been identified that cure the human body from a number of diseases. The present article reviews the potential efficacy of plant-derived alkaloids, which possess potential therapeutic effects against several NDDs including Alzheimer's disease (AD), Huntington disease (HD), Parkinson's disease (PD), Epilepsy, Schizophrenia, and stroke. Alkaloids include isoquinoline, indole, pyrroloindole, oxindole, piperidine, pyridine, aporphine, vinca, ß-carboline, methylxanthene, lycopodium, and erythrine byproducts. Alkaloids constitute positive roles in ameliorating pathophysiology of these illnesses by functioning as muscarinic and adenosine receptors agonists, anti-oxidant, anti-amyloid and MAO inhibitors, acetylcholinestrase and butyrylcholinesterase inhibitor, inhibitor of α-synuclein aggregation, dopaminergic and nicotine agonist, and NMDA antagonist.